Thrombotic complications comprise a significant amount of the problems in the clinical use of valve prostheses. One factor attributed to the initiative processes leading to thrombus formation is the dynamics of the flow in the vicinity of the thrombus formation site. The aims of the proposed research program are to analyze the direct effect of fluid dynamics on thrombosis of blood, with particular application to blood flow through prosthetic mitral valves in the left ventricle. To be tested is the interaction between areas of high shear, areas of recirculation, areas of stagnation, and unsteadiness of flow and to what extent each or combinations of these flow phenomena is necessary for thrombus formation in blood. The study will consist of two phases. Phase I will be a fundamental approach by analyzing the flow in various geometries of flow chambers in both steady and pulsatile flow loops. These flow chambers will create different combinations of these flow phenomena. The flow analysis will be accomplished by experimental means using laser Doppler anemometry to measure velocity and turbulence as well as numerical methods to determine the details of the flow dynamics. These results will be compared to sites of thrombus formation and deposition determined by In-Ill labeling of platelets in pig blood flowing through similar models in vitro. Phase II will use the knowledge gained from Phase I to predict sites of thrombosis in flow past prosthetic mitral valves in the left ventricle. A numerical model simulating blood flow, both laminar and turbulent, in the left ventricle during diastole will be developed, which can be used to quantify the detailed flow dynamics in the vicinity of various geometries of mitral valve prostheses. The type of flow dynamics produced by a prosthetic mitral valve include those studied in Phase I. Therefore, from the fundamental correlations determined from Phase I between thrombus formation and various combinations of flow phenomena, an evaluation of the flow produced by the mitral valve will be made for possible problem sites of thrombus formation. The overall goal of this study is to analyze for design improvements to minimize problems of thrombus formation.